BRENDA - Enzyme Database show
show all sequences of 2.7.11.30

Reduced SMAD7 leads to overactivation of TGF-beta signaling in MDS that can be reversed by a specific inhibitor of TGF-beta receptor I kinase

Zhou, L.; McMahon, C.; Bhagat, T.; Alencar, C.; Yu, Y.; Fazzari, M.; Sohal, D.; Heuck, C.; Gundabolu, K.; Ng, C.; Mo, Y.; Shen, W.; Wickrema, A.; Kong, G.; Friedman, E.; Sokol, L.; Mantzaris, I.; Mantzaris, G.; Pellagatti, A.; Boultwood, J.; Platanias, L.C.; Steidl, U.; Yan, L.; Yingling, J.M.; Lahn, M.M.; Cancer Res. 71, 955-963 (2011)

Data extracted from this reference:

Application
Application
Commentary
Organism
medicine
therapeutic potential of TBRI inhibitors in myelodysplastic syndrome, MDS. The myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by cytologic dysplasia and ineffective hematopoiesis
Homo sapiens
Inhibitors
Inhibitors
Commentary
Organism
Structure
LY-2157299
LY-2157299 inhibits TGF-beta mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells. In vivo administration of LY-2157299 ameliorates anemia in a TGF-beta overexpressing transgenic mouse model of bone marrow failure. Treatment with LY-2157199 stimulates hematopoiesis from primary myelodysplastic syndrome bone marrow specimens
Homo sapiens
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
P36897
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
bone marrow
-
Homo sapiens
-
HS-5 cell
-
Homo sapiens
-
K-562 cell
-
Homo sapiens
-
Application (protein specific)
Application
Commentary
Organism
medicine
therapeutic potential of TBRI inhibitors in myelodysplastic syndrome, MDS. The myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by cytologic dysplasia and ineffective hematopoiesis
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
LY-2157299
LY-2157299 inhibits TGF-beta mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells. In vivo administration of LY-2157299 ameliorates anemia in a TGF-beta overexpressing transgenic mouse model of bone marrow failure. Treatment with LY-2157199 stimulates hematopoiesis from primary myelodysplastic syndrome bone marrow specimens
Homo sapiens
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
bone marrow
-
Homo sapiens
-
HS-5 cell
-
Homo sapiens
-
K-562 cell
-
Homo sapiens
-
General Information
General Information
Commentary
Organism
malfunction
reduction in SMAD7 can lead to increased sensitivity to suppressive effects of TGF-beta on hematopoiesis. SMAD7, a negative regulator of TGF-beta receptor I (TBRI) kinase is markedly decreased in a large meta-analysis of gene expression studies from myelodysplastic syndrome marrow derived CD34+ cells, SMAD7 protein is also significantly decreased in myelodysplastic syndrome marrow progenitors. The increased TGF-beta signaling due to SMAD7 reduction can be effectively inhibited by TBRI (ALK5 kinase) inhibitor LY-2157299
Homo sapiens
physiological function
SMAD7 is a negative regulator of TGF-beta receptor I (TBRI) kinase. The enzyme increases Smad7 via increased TGF-beta signaling
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
malfunction
reduction in SMAD7 can lead to increased sensitivity to suppressive effects of TGF-beta on hematopoiesis. SMAD7, a negative regulator of TGF-beta receptor I (TBRI) kinase is markedly decreased in a large meta-analysis of gene expression studies from myelodysplastic syndrome marrow derived CD34+ cells, SMAD7 protein is also significantly decreased in myelodysplastic syndrome marrow progenitors. The increased TGF-beta signaling due to SMAD7 reduction can be effectively inhibited by TBRI (ALK5 kinase) inhibitor LY-2157299
Homo sapiens
physiological function
SMAD7 is a negative regulator of TGF-beta receptor I (TBRI) kinase. The enzyme increases Smad7 via increased TGF-beta signaling
Homo sapiens
Other publictions for EC 2.7.11.30
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
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Homo sapiens
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Homo sapiens
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Ovis aries
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664721
Zhang
Activin receptor-like kinase 7 ...
Rattus norvegicus
Diabetologia
49
506-518
2006
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664088
Peng
Kinetic characterization of no ...
Homo sapiens
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664715
Desgrosellier
Activin receptor-like kinase 2 ...
Gallus gallus
Dev. Biol.
280
201-210
2005
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665640
Ungefroren
Transforming growth factor-bet ...
Homo sapiens
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280
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2005
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665699
Lux
Human retroviral gag- and gag- ...
Homo sapiens
J. Biol. Chem.
280
8482-8493
2005
1
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666443
Halder
A specific inhibitor of TGF-be ...
Homo sapiens
Neoplasia
7
509-521
2005
1
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663984
Ge
Selective inhibitors of type I ...
Homo sapiens
Biochem. Pharmacol.
68
41-50
2004
2
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1
1
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3
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3
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1
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1
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664036
Ottesen
Semisynthesis of phosphovarian ...
Homo sapiens
Biochemistry
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2
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1
2
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2
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2
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4
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1
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1
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1
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2
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4
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1
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1
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664318
Sawyer
Synthesis and activity of new ...
Homo sapiens, Mus musculus
Bioorg. Med. Chem. Lett.
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3581-3584
2004
2
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1
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6
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2
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2
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2
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1
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2
-
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2
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2
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2
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2
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6
2
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1
2
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6
6
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2
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2
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1
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2
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2
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2
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2
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665532
Kim
Activin receptor-like kinase-7 ...
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1
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1
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3
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1
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1
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3
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2
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5
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1
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1
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1
1
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3
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1
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1
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2
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5
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665554
Yakymovych
Smad2 phosphorylation by type ...
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J. Biol. Chem.
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35781-35787
2004
1
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1
2
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2
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1
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2
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5
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1
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1
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1
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1
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1
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1
2
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2
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2
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5
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1
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1
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666283
Forrester
Tegumental expression of a nov ...
Schistosoma mansoni
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149-156
2004
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1
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1
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4
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1
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1
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4
-
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666359
Mazerbourg
Growth differentiation factor- ...
Rattus norvegicus
Mol. Endocrinol.
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653-665
2004
2
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1
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1
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2
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1
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3
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2
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3
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4
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1
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2
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1
1
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1
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1
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3
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3
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4
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664282
Roberts
Identification of novel isofor ...
Homo sapiens
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1719-1726
2003
2
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1
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1
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1
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2
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8
-
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2
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1
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1
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1
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8
-
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665481
Liu
Smads 2 and 3 are differential ...
Rattus norvegicus
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1
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5
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1
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1
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5
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665487
Harrison
Identification of a functional ...
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2
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1
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27
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1
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1
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1
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-
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1
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1
1
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-
-
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1
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2
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1
1
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27
-
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1
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1
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1
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1
1
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666312
Goumans
Activin receptor-like kinase ( ...
Mus musculus
Mol. Cell
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817-828
2003
2
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1
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1
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1
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1
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1
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1
1
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5
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1
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2
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1
1
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1
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1
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1
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5
-
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1
1
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5
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666512
Fink
TGF-beta-induced nuclear local ...
Homo sapiens
Oncogene
22
1317-1323
2003
1
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1
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3
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1
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5
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5
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1
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1
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1
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5
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